Among the plethora of chemotherapeutic agents in use at this time for the treatment of solid tumors, metastatic conditions, and leukemias, adriamycin and its analogs are among the most prominent. Adriamycin is a commercial name for doxorubicin, which is a polycyclic naphthacene-based glycoside of the deoxyamino sugar, daunosamine. A class of similar compounds, which are also glycosides of daunosamine, but which contain polycyclic systems related to anthracene, is represented by ametantrone and mitoxantrone. This class also has powerful anti-tumor activity.
It has been suggested that the C-glycoside analogs of these anti-tumor compounds might have some advantageous properties in connection with their therapeutic use. It is known that adriamycin and its analogs are inactivated by de-glycosidation. It is expected that though the C-glycoside analogs would be resistant to this degradation, as they are isosteric to compounds of known anti-tumor activity, they should be effective in analogous therapeutic ways. Acton, E. M., et. al, Carbohydrate Research (1981) 97:235-245 suggested a synthetic pathway for the preparation of such C-glycosidic analogs, but the reaction pathway suggested has since been shown not to yield the expected products. Therefore, although the goal was stated, the means for attaining it have not been available in the art.
The present invention provides a general means for obtaining essential intermediates in the production of the desired C-glycosides. It is also of general use in obtaining pentadienyl and acetaldehyde derivatives of 2-deoxypyranose sugars.